Tuberculosis Among Native Hawaiian and Other Pacific Islander Persons: United States and U.S.-Affiliated Pacific Islands, 2010–2019

Background: In recent years, tuberculosis (TB) incidence in the United States has declined overall but remained high among Native Hawaiian and Other Pacific Islander (NH/PI) persons. Few studies have examined the epidemiology of TB among NH/PI persons, particularly in the U.S.-Affiliated Pacific Islands (USAPI). We describe TB incidence and characteristics of NH/PI patients during 2010–2019. Methods: We used data from the National Tuberculosis Surveillance System to characterize TB cases reported among NH/PI persons born in the 50 U.S. states (defined to include District of Columbia) and the USAPI. We calculated annual TB incidence among NH/PI patients, stratified by place of birth (U.S. states or USAPI). Using Asian persons born outside the United States—persons historically grouped with NH/PI persons as one racial category—as the reference, we compared demographic, clinical, and socio-behavioral characteristics of NH/PI TB patients. Results: During 2010–2019, 4359 TB cases were reported among NH/PI patients born in the U.S. states (n=205) or the USAPI (n=4154). Median annual incidence per 100,000 persons was 6.5 cases (persons born in the U.S. states) and 150.7 cases (persons born in the USAPI). The proportion of TB patients aged <15 years was higher among NH/PI persons (U.S. states: 54%, USAPI: 24%) than among Asian persons born outside the United States (1%). Conclusions: TB incidence among NH/PI persons is high, particularly among persons born in the USAPI, emphasizing the need to enhance TB prevention strategies in these communities. Interventions should be tailored toward those who experience the highest risk, including NH/PI children and adolescents.


Introduction
Although overall tuberculosis (TB) incidence has declined in the United States in recent years, incidence among Native Hawaiian and Other Pacific Islander (NH/PI) persons residing in the United States at the time of their TB diagnosis has remained high. 1 In addition, TB incidence in the U.S.-Affiliated Pacific Islands (USAPI) is higher than in the United States. 1 Some NH/PI populations experience higher rates of infectious diseases (such as sexually transmitted diseases and Hansen's disease), 2-4 diabetes, and infant mortality, and they have lower life expectancy compared with non-Hispanic White persons. 5,6 Similarly, social determinants of health, including educational attainment, income, and health insurance coverage, are all lower among NH/PI persons than among non-Hispanic White persons. 5,7,8 Despite these inequities, a few epidemiologic studies have examined TB among NH/PI persons, and TB in the USAPI specifically. 9,10 Additional work to characterize the disproportionately high rates of TB disease among NH/PI persons is needed to inform tailored public health interventions that reduce incidence in this population. 1,7 Given the differences in TB incidence between the USAPI and the 50 U.S. states, understanding the epidemiology of both regions is important for designing and implementing effective TB control measures. In addition, TB disease in the United States is strongly influenced by place of birth. 1 The USAPI (comprising six areas: Guam, the Commonwealth of the Northern Mariana Islands, American Samoa, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau) conduct TB surveillance in partnership with the Centers for Disease Control and Prevention (CDC). However, detailed published data regarding TB in the USAPI are limited; to our knowledge, no studies of TB disease in NH/PI populations have explored differences in TB epidemiology by place of birth.
In this analysis, we compared disease incidence associated with, and demographic and clinical characteristics of, NH/PI TB patients born in the 50 states or DC and those born in the USAPI. We stratified our analysis by place of birth (U.S. states or USAPI) to understand TB epidemiology within populations with substantially different baseline risks for TB.

National Tuberculosis Surveillance System
We analyzed TB case data from the National Tuberculosis Surveillance System (NTSS), a database maintained by the CDC. NTSS reporting areas comprise all 50 states, the District of Columbia (DC), New York City, Puerto Rico, the U.S. Virgin Islands, and the six USAPI regions. Each reporting area submits case reports containing standardized demographic and clinical data elements for each verified TB case to NTSS. 1 This project was determined not to be human subjects research by the CDC and did not require approval by an institutional review board, because data were collected and analyzed as part of routine public health surveillance.

Population
Our analyses included a subset of all incident TB cases reported to NTSS during January 1, 2010-December 31, 2019 and counted in any of the 50 states or Washington, DC or any of the six USAPI areas.
The TB patients were categorized as Hispanic (regardless of patient race) or non-Hispanic based on patient self-reported ethnicity. 11 Cases in patients not reporting Hispanic ethnicity were then further categorized by self-reported race into standard federal race categories: American Indian/Alaska Native, Asian, Black/African-American, NH/PI, White, and multiple race. 11 Following previous studies of TB among NH/ PI persons, 9,12 persons reporting ‡ 1 race or Hispanic ethnicity were not included in the NH/PI category.
The analysis population included and was determined by categorizing cases as one of four analytic groups using patient self-reported race, ethnicity, and place of birth: non-Hispanic single-race NH/PI TB patients born in the 50 states or DC (hereafter, ''NH/ PI 50 states''), non-Hispanic single-race NH/PI patients born in the USAPI (''NH/PI USAPI''), non-Hispanic single-race Asian patients born in Asia { , (''Asian''), and non-Hispanic single-race White patients born in the 50 states or DC (''White'').
Because Asian persons born in the U.S. states constituted < 5% of all Asian TB patients, and experience substantially lower TB risk, 1

Statistical analyses
We enumerated annual incidence (cases per 100,000 persons) by analytic group using estimates of annual group population size obtained from multiple data sources (e.g., U.S. Census Bureau's American Community Survey, U.S. Census Bureau's International Database, United Nations World Population Prospects). 14- 16 We calculated annual incidence for each of the four groups described earlier as well as for each of the USAPI regions. These latter calculations included all cases in NH/PI patients who were born in the USAPI and reported as a verified TB case anywhere in the USAPI. We also calculated incidence for the NH/PI 50 states analytic group among the U.S. Department of Health and Human Services (HHS) Region. 17 Additional methods regarding the population data sources and incidence calculations are provided in Supplementary File S1.
We compared the annual TB incidence among analytic groups by calculating the incidence rate ratio (IRR) and associated 95% confidence intervals (CI). Our primary comparisons used the Asian analytic group as the reference. We used the White analytic group as a reference for secondary analyses (additional information is provided in Supplementary File S1). We calculated CIs using the normal approximation (Wald) method if the numerator for any group calculation was > 10 and otherwise using a bootstrap method with 10,000 replicates.
We compared the distributions of demographic and clinical characteristics of TB disease between the NH/PI analytic groups and the Asian group by using chi-squared tests or Fisher's exact tests (for proportions with numerators < 10). We further analyzed selected clinical and sociodemographic characteristics of disease among patients aged ‡ 15 by comparing the prevalence of each patient characteristic among groups using a bivariate prevalence ratio (PR) and associated 95% CI.
Additional details regarding the definitions of these characteristics are available in Supplementary File S1. As with the incidence comparisons, we used the Asian analytic group as the reference for our primary analyses. We calculated the 95% CIs as described earlier. We defined statistical significance using an alpha level of 0.05. Additional details regarding the methods for these calculations are provided in Supplementary File S1.

Case counts
During 2010-2019, 101,209 incident TB cases were reported to NTSS. Of these, 4,359 (4%) were in NH/ PI patients born in the U.S. states or USAPI: 205 (4.7%) in NH/PI 50 states patients and 4,154 (95.3%) in NH/PI USAPI patients (Table 1). Three hundred forty-one TB cases in NH/PI patients born in countries other than the United States or the USAPI were excluded from the analyses (Supplementary Table S1). The Asian and White analytic groups contained 29,901 (30% of total) and 10,119 (10% of total) cases, respectively.

Incidence
Median annual incidence (cases per 100,000 persons) in the NH/PI USAPI group was 150.7, (range = 123. Compared with the White group, incidence was consistently higher for both NH and PI analytic groups.

Discussion
We found a high incidence of TB among NH/PI persons, particularly among patients born in the USAPI. The higher incidence of TB among NH/PI persons born in the USAPI compared with the NH/PI persons born in 50 states highlights the historically high incidence in the USAPI and the need to enhance TB control and prevention efforts in the USAPI. The NH/PI persons composed *0.3% of the combined U.S. and USAPI populations during the investigation period 15,18 yet 4% of reported TB cases. These findings further emphasize the previously reported higher incidence of TB among indigenous populations compared with persons of other racial and ethnic groups 9,10,12 and the need to address the documented health disparities associated with NH/PI populations. [2][3][4]6 In addition, these findings expand on this previous work focused on persons born in the United States 9 by exploring TB epidemiology among persons born in the USAPI.  Focusing efforts on TB prevention among NH/PI children is critical. The proportions of TB cases among children aged < 15 years observed in this analysis were higher among NH/PI 50 states (54%) and NH/PI USAPI patients (24%) than among all persons with TB in the United States (5%). 1 Children < 5 are more likely to develop TB disease once infected and therefore pediatric infections represent an indicator of recent TB transmission. 19,20 The markedly higher proportion of pediatric NH/PI TB patients supports previous findings of a high level of recent transmission among NH/PI persons living in the United States at the time of their TB diagnosis; more than a third of TB cases among NH/PI persons were attributed to recent transmission in 2019-2020. 1 This finding also has important implications for TB surveillance. The high proportion of children with TB may contribute to the lower overall proportion of culture-positive cases among NH/PI patients observed here, and in previous studies, 21 because TB in children is less likely to be culture confirmed. 22 Fewer culture-confirmed TB cases hamper surveillance efforts based on genomic sequencing, which uses an isolate from culture. 23 The high incidence of TB among NH/PI persons is particularly notable considering the low prevalence ( < 1%) of HIV in this population. This finding is in contrast with many other populations globally, where HIV co-infection is a primary driver of TB disease. 24,25 Instead, the high incidence of TB among NH/PI persons may be driven by higher rates of TB exposure and contributed to by the high prevalence of diabetes in this analysis. We observed an overall diabetes prevalence of 26% among NH/PI TB patients ‡ 15 years; the U.S. national estimate of diabetes prevalence among single-race NH/PI adults is *18% 26 whereas the prevalence among all adults in the Western Pacific Region of the world (which includes the USAPI) is *10%. 27 As diabetes is associated with more severe TB disease outcomes, 28 the diabetes comorbidity has important implications for TB control and prevention programs that otherwise generally focus attention and resources on the role of HIV.
Compared with the Asian adult group, the relatively higher prevalence of drug use and excess alcohol use among NH/PI TB adult patients also has important implications for management of TB disease. Similar to diabetes, injection drug use is a known risk factor for progression to TB among persons who are infected. 29 Persons who use substances can also face challenges when obtaining medical attention and completing TB treatment. 30, 31 The geographic variation we observed points to regions where TB prevention efforts focused on NH/PI persons would be most appropriate. HHS Region 6 (Arkansas, Louisiana, New Mexico, Oklahoma, and Texas), which had the highest median incidence of TB among NH/PI TB patients in the 50 states, has a large population of NH/PI persons, with several counties in which NH/PI persons compose > 1% of the population. 32 These findings further highlight jurisdictions in need of additional TB support for NH/PI communities.
The steep increase in TB cases found in the Republic of the Marshall Islands beginning in 2017-2019 coincides with multiple mass screening events that were conducted starting in 2017. 33,34 Active case finding might be a useful tool for interrupting the spread of M.Tb in areas of high TB incidence with ongoing transmission. In addition, public health partners and local clinical care providers in these areas should consider whether NH/PI persons may benefit from enhanced TB prevention efforts. The U.S. Preventive Services Task Force and CDC recommend routine latent TB infection screening for persons who experience the highest risk, including those who have lived in areas of increased TB prevalence. 35 This analysis is subject to several limitations. First, the denominator population data used to calculate incidence were drawn from multiple sources, limiting our ability to compare incidence estimates across the regions. Similarly, population estimates for members of racial and ethnic minority groups, such as NH/PI persons, may be less reliable due to smaller population sizes. Second, we excluded NH/PI persons of multiple race, which may have affected our findings. Third, our statistical analysis was restricted to bivariate associations and cannot be interpreted as causal relationships. Lastly, the low number of observations, particularly among the NH/PI 50 states group, yields variable incidence estimates that are subject to yearly fluctuation.

Health equity implications
The numerous differences in the characteristics of NH/PI TB patients compared with Asian TB patientstwo racial groups previously classified as one 36 demonstrate the importance of selecting an appropriate reference group when conducting epidemiologic analyses. Though the two groups have been disaggregated in NTSS since 2003, 1 our analysis demonstrates differences in the epidemiology of TB among these populations and supports the previously documented need for more detailed analyses among members of different racial and ethnic groups. 8 Detailed analyses such as this are particularly critical when exploring issues of health equity, as aggregating groups may hide key differences in a disease's incidence or experiences with risk factors.
These findings contribute to the body of evidence describing health disparities among NH/PI communities. To our knowledge, this is the first study to compare TB epidemiology between NH/PI persons born in the 50 states or Washington, DC and NH/PI persons born in the USAPI. This work highlights important differences in the epidemiology of TB by place of birth, demonstrating the need for TB interventions that appropriately address the needs of these different populations. Interventions that address social determinants of health, such as homelessness, may help reduce TB incidence among NH/PI populations. In addition, active TB screenings among persons born in the USAPI and efforts to increase TB treatment completion may help reduce TB transmission among NH/PI communities.